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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2474-2483. Prepublished online as a Blood First Edition Paper on June 23, 2008; DOI 10.1182/blood-2007-12-130211. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-12-130211v1 112/6/2474    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhou, Y. Articles by Pang, Q. Search for Related Content PubMed PubMed Citation Articles by Zhou, Y. Articles by Pang, Q. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA TAT-mediated intracellular delivery of NPM-derived peptide induces apoptosis in leukemic cells and suppresses leukemogenesis in mice Yun Zhou1,*, Wei Du1,*, Tara Koretsky2, Grover C. Bagby2, and Qishen Pang1,3 1 Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, OH; 2 Oregon Health and Science University (OHSU) Cancer Institute, Portland; and 3 Department of Pediatrics, University of Cincinnati College of Medicine, OH Nucleophosmin (NPM) is frequently overexpressed in leukemias and other tumors. NPM has been reported to suppress oncogene-induced senescence and apoptosis and may represent a therapeutic target for cancer. We fused a NPM-derived peptide to the HIV-TAT (TAT-NPMC) and found that the fusion peptide inhibited proliferation and induced apoptotic death of primary fibroblasts and preleukemic stem cells. TAT-NPMC down-regulated several NF-B–controlled survival and inflammatory proteins and suppressed NF-B–driven reporter gene activities. Using an inflammation-associated leukemia model, we demonstrate that TAT-NPMC induced proliferative suppression and apoptosis of preleukemic stem cells and significantly delayed leukemic development in mice. Mechanistically, TAT-NPMC associated with wild-type NPM proteins and formed complexes with endogenous NPM and p65 at promoters of several antiapoptotic and inflammatory genes and abrogated their transactivation by NF-B in leu-kemic cells. Thus, TAT-delivered NPM peptide may provide a novel therapy for inflammation-associated tumors that require NF-B signaling for survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Pabst and B. U. Mueller Complexity of CEBPA Dysregulation in Human Acute Myeloid Leukemia Clin. Cancer Res., September 1, 2009; 15(17): 5303 - 5307. [Abstract] [Full Text] [PDF] S. Koschmieder, B. Halmos, E. Levantini, and D. G. Tenen Dysregulation of the C/EBP{alpha} Differentiation Pathway in Human Cancer J. Clin. Oncol., February 1, 2009; 27(4): 619 - 628. [Abstract] [Full Text] [PDF]

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